Brain regional α-[<Superscript>11</Superscript>C]methyl-<Emphasis Type="SmallCaps">L</Emphasis>-tryptophan trapping,used as an index of 5-HT synthesis,in healthy adults: absence of an age effect

Purpose Previous functional neuroimaging studies suggest that selective aspects of the brain serotonin (5-HT) system change during the aging process. Here, we assessed the effects of aging on the brain regional α-[¹¹C]methyl-L-tryptophan (α-[¹¹C]MTrp) trapping rate constant (K*; μl·g⁻¹·min⁻¹), which, with certain assumptions, could be taken as a proxy of 5-HT synthesis. Methods Thirty-six healthy right-handed subjects had positron emission tomography (PET) scans following injection with α-[¹¹C]MTrp [18 males aged 46.6 ± 22.2 years (range 20–80 years) and 18 females aged 33.0 ± 15.5 years (range 20–80 years)]. The trapping rate constant, K*, was calculated with the graphical method for irreversible ligands using the sinus-venous input function. A priori selected volumes of interest (VOIs) were defined using an automatic algorithm. Results VOI analysis showed no correlation between age and brain regional K* values. As reported by others, significant age-related reductions of gray matter were observed in the thalamus and frontal and cingulate cortices; even with partial volume correction there was still no significant relationship between K* and age. Further exploratory SPM voxelwise correlation between age and α-[¹¹C]MTrp trapping, using p = 0.05 (uncorrected), as well as voxel-based morphometry, was in agreement with the VOI analysis. Conclusion The dissociation between age-related changes in brain anatomy and this index of serotonin synthesis suggests independent mechanisms underlying the normal aging process.     

Flavonoids,cytotoxic, antioxidant and antibacterial activities of Evax pygmaea

Context: Phytochemical study and biological potential of Evax pygmaea (L.) Brot. (Asteraceae) are reported for the first time.

Objective: To identify the secondary metabolites of Evax pygmaea and to determine its antioxidant, antibacterial and cytotoxic activities.

Materials and methods: Dried aerial parts (1?kg) were macerated in 70% MeOH (5?L) during 72?h. The concentrated hydromethanolic extract was subjected to extractions with chloroform (3?×?300?mL), ethyl acetate (3?×?300?mL) and n-butanol (3?×?300?mL), successively. VLC of combined ethyl acetate (EAEP) and n-butanol (BEP) fractions was followed by column purifications. Antioxidant activity was investigated using DPPH, CUPRAC, and metal chelating, β-carotene/linoleic acid and ABTS assays. Agar method was used in the antibacterial study. Cytotoxic activity was determined by Brine shrimp lethality test in DMSO and ethanol, at varying concentrations (2, 1 and 0.2%) and (1, 0.2 and 0.1%) successively.

Results: Quercetin (1), isorhamnetin 3-O-β-d-xyloside (2), isorhamnetin 3-O-β-d-glucoside (3), quercetin 3-O-β-d-glucoside (4), quercetin 7-O-β-D-glucoside (5), patuletin 3-O-β-d-glucoside (6) were isolated from for the first time from Evax genus. The EAEP was the most active in ABTS (IC₅₀: <3.125?μg/mL) assay whereas the BEEP exhibited the highest activity in the β-carotene/linoleic acid assay (IC₅₀: <3.125?μg/mL). The EAEP and BEP exhibited good antibacterial activity (MIC: 40–80 µg/mL). The plant did not show any toxicity (LD₅₀>80 µg/mL).

Discussion and conclusions: Six flavonoids were isolated for the first time from Evax pygmaea which exhibited good antioxidant and antibacterial activities.     

Epidemiologic investigation of Burkholderia cepacia acquisition in two pediatric intensive care units.

OBJECTIVES: To investigate and describe an outbreak of Burkholderia cepacia in a neonatal intensive care unit (NICU) and a pediatric intensive care unit (PICU), and to report the interventions leading to the cessation of the outbreak. DESIGN: We conducted an epidemiologic investigation of an outbreak of B. cepacia colonization or infection in two clinical wards during a 35-month period (December 1998 to October 2001). SETTING: A 500-bed, university hospital-affiliated, tertiary-care pediatric institution in Paris, France, with a 22-bed PICU and 31-bed NICU. METHODS: Ribotyping was used to determine the genotypes of B. cepacia isolates. Procedures for the maintenance and disinfection of respiratory therapy devices were reviewed. RESULTS: Thirty-two children were colonized (n = 14) or infected (n = 18) by B. cepacia in 2 wards (28 in the PICU and 4 in the NICU). In the PICU, a single ribotype was found among the isolates obtained from all of the patients except 1, and from the 6 isolates obtained from respiratory therapy devices (ie, heated humidifier water). In the NICU, the isolates obtained from the patients harbored a single ribotype unrelated to that of the epidemic strain isolated in the PICU; no environmental source of infection was found. CONCLUSION: Two different outbreaks appeared to be associated with 2 ribotypes, 1 of which was linked to patient-to-patient transmission via respiratory therapy devices. Complete elimination of the outbreak was achieved only when disposable, sterilizable, or easy-to-disinfect materials were used in the PICU. The source of infection in the NICU was not found.     

Coronary surgery of the beating heart. First year of experience in a series of 317 non-selected coronary patients

From May 1999 to May 2000, 317 unselected patients, representing 92.7% of all coronary artery surgery procedures, underwent open heart surgery of the beating heart by median sternotomy with the aid of a cardiac stabilising device. The main preoperative characteristics were: mean age = 66.1 years; men = 78.9%; left main stem disease = 31.8%; mean left ventricular ejection fraction = 54.1%; mean Parsonnet index = 16.9. These 317 patients were compared with a group of 303 patients who underwent coronary bypass surgery the year before by the same surgical team with cardiopulmonary bypass (CPB) and cardiac standstill. Seven hundred and eighty-six distal anastomoses were carried out in the beating heart group (2.48 grafts per patient) compared with 2.91 in the CPB group: p < 0.001). There were 10.1% single bypass, 37.5% double bypass, 47.3% triple bypass and 5% quadruple bypass procedures. A cardiopulmonary bypass was required in 13 patients (4.1%). The mortality at 30 days was 3.1% versus 4.6% in the CPB group (p = NS). The need for blood transfusion was reduced by nearly 40% in the beating heart group (23.7% versus 39.9%, p < 0.001). The incidence of cerebrovascular complications was reduced from 3% in the CPB group to 0.6% in the beating heart group (p = 0.06). The peak postoperative troponine I levels were much lower in the beating heart group (2.5 versus 6.4 ng/ml, p < 0.001). The authors conclude that surgery on the beating heart is feasible in most patients. Compared with conventional surgery under CPB, there seems to be less requirement for blood transfusion and a tendency to reduce the cerebral risk. Nevertheless, a large prospective randomised trial is required to validate the potential advantages and limitations of this technique with respect to conventional surgery and to determine the optimal indications of surgery on the beating heart.     

Medication Errors in the Management of Anaphylaxis in a Pediatric Emergency Department

Background

Despite the publication of recent guidelines for anaphylaxis management, many studies show that physicians are still not at ease with the management of anaphylaxis.

Objectives

To evaluate the rate and severity of medication errors before and after implementation of a standard order form for anaphylaxis management.

Methods

A before-and-after study was conducted. All children <18 years of age presenting to a tertiary care pediatric hospital Emergency Department with anaphylaxis between September 2007 and November 2010 were included. Patients were divided into two groups according to intervention (Pre and Post). Intervention consisted of the implementation of a standard order form (SOF) for anaphylaxis management. The post-intervention group was further sub-divided into SOF+ (when the SOF was used) and SOF− (when the SOF was not used).

Results

A total of 96 medical charts were reviewed. There were 31 patients in Pre and 65 in Post (29 in SOF+ and 36 in SOF−). A total of 243 drugs were ordered. Thirty-five percent (85/243) of these orders contained at least one medication error. Fifty-five percent (47/85) were dosage errors. The rate of medication errors was the same between Pre and Post (60% vs. 59%, p = 0.95). However, the rate of dosage errors was significantly reduced when the SOF was used (21% in SOF+ vs. 50% in Pre, p = 0.02 and 21% in SOF+ vs. 50% in SOF−, p = 0.02).

Conclusions

Medication errors in the management of anaphylaxis were frequent. Use of an SOF significantly reduced the rate of dosage errors.     

Mood stability during acute stimulator challenge in Parkinson's disease patients under long-term treatment with subthalamic deep brain stimulation.

Acute and chronic behavioral effects of subthalamic stimulation (STN-DBS) for Parkinson's disease (PD) are reported in the literature. As the technique is relatively new, few systematic studies on the behavioral effects in long-term treated patients are available. To further study the putative effects of STN-DBS on mood and emotional processing, 15 consecutive PD patients under STN-DBS for at least 1 year, were tested ON and OFF stimulation while on or off medication, with instruments sensitive to short-term changes in mood and in emotional discrimination. After acute changes in experimental conditions, mood core dimensions (depression, elation, anxiety) and emotion discrimination processing remained remarkably stable, in the face of significant motor changes. Acute stimulator challenge in long-term STN-DBS-treated PD patients does not appear to provoke clinically relevant mood effects.     

Effect of tryptophan hydroxylase-2 gene variants on suicide risk in major depression.

BACKGROUND: Suicide and depressive disorders are strongly associated, yet not all depressed patients commit suicide. Genetic factors may partly explain this difference. We investigated whether variation at the tryptophan hydroxylase-2 (TPH2) gene and its 5' upstream region may predispose to suicide in major depressive disorder (MDD) and whether this predisposition is mediated by impulsive-aggressive behaviors (IABs). METHODS: We genotyped 14 single nucleotide polymorphisms (SNPs) in 259 depressed subjects, 114 of which committed suicide while depressed. Phenotypic assessments were carried out by means of proxy-based interviews. Single-marker and haplotype association analyses were conducted. Differences in behavioral and personality traits according to genotypic variation were investigated, as well as genetic and clinical predictors of suicide. RESULTS: We found two upstream and two intronic SNPs associated with suicide. No direct effect of these variants was observed on IABs. However, a slight association with reward dependence scores was found. Controlling for suicide risk factors, two SNPs (rs4448731 and rs4641527) significantly predicted suicide, along with cluster B personality disorders and family history of suicide. CONCLUSIONS: The TPH2 gene and its 5' upstream region variants may be involved in the predisposition to suicide in MDD; however, our findings do not support the role of IABs as mediators.